NCT00770471

ABT-888, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

A Phase I/II Trial of Temozolomide and ABT-888 in Subjects With Newly Diagnosed Glioblastoma Multiforme

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ABT-888 together with radiation therapy and temozolomide may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of ABT-888 when given together with radiation therapy and temozolomide and to see how well it works in treating patients with newly diagnosed glioblastoma multiforme.

Detailed description

OBJECTIVES: Primary * To determine the maximum tolerated dose (MTD) of ABT-888 when administered in combination with radiotherapy and temozolomide in patients with newly diagnosed glioblastoma multiforme. (Phase I) * To estimate the overall survival of patients treated with ABT-888 when administered at the MTD in combination with radiotherapy and temozolomide. (Phase II) Secondary * To assess the toxicity associated with this regimen. (Phase I) * To assess and describe the pharmacokinetics of ABT-888. (Phase I) * To estimate the frequency of toxicity associated with this regimen. (Phase II) OUTLINE: This is a multicenter, phase I dose-escalation study of ABT-888 followed by a phase II study. * Initiation therapy: Patients receive oral ABT-888 twice daily (once on day 1 only) and oral temozolomide once daily (beginning on day 2) in weeks 1-6. Patients enrolled in the phase I dose-escalation/phase II portion of the study also undergo concurrent radiotherapy once daily 5 days a week (beginning on day 2) in weeks 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity. * Maintenance therapy: Beginning 4 weeks after completion of initiation therapy, patients receive oral ABT-888 twice daily on days 1-7 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 4 courses (6 courses for patients enrolled in the phase I dose-escalation/phase II portion of the study) in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for pharmacokinetic, pharmacogenetic, and pharmacodynamic analysis. Samples are analyzed for concentration of ABT-888 in plasma by reversed-phase isocratic high performance liquid chromatography with electrospray ionization mass spectrometry; identification of novel markers of treatment response by plasma proteomic evaluation; DNA methylation and/or mutation; and PARP inhibition by ELISA. After completion of study therapy, patients are followed every 2 months.

Conditions

• Brain and Central Nervous System Tumors

Interventions

Type	Name	Description
DRUG	temozolomide
DRUG	veliparib
GENETIC	DNA methylation analysis
GENETIC	gene expression analysis
GENETIC	mutation analysis
GENETIC	proteomic profiling
OTHER	high performance liquid chromatography
OTHER	immunoenzyme technique
OTHER	laboratory biomarker analysis
OTHER	mass spectrometry
OTHER	pharmacogenomic studies
OTHER	pharmacological study
PROCEDURE	adjuvant therapy
RADIATION	radiation therapy

Timeline

• Start date: 2009-07-13
• Primary completion: 2012-03-01
• Completion: 2012-03-01
• First posted: 2008-10-10
• Last updated: 2018-06-27

Locations

11 sites across 1 country: United States

Regulatory

• FDA-regulated drug study